The integrated function of dopaminergic, GABAergic and Substance P neurons was investigated in striatum and N. accumbens after short-and long-term treatment with antischizophrenic drugs. The data suggest that GABA and Substance P terminals in SN may be involved in mediating the effect of antischizophrenic drugs on nigro-striatal DA system. Long-term treatment with classical (cataleptogenic) antischizophrenic drugs produces tolerance to the activation of the DA striatal system. Tolerance is not observed after long-term treatment with atypical (non-cataleptogenic) antischizophrenic drugs. These data suggest that antischizophrenic drug-induced tolerance of the DA system in striatum is associated with DA receptor supersensitivity.